System and method for pacing rate control utilizing patient hemodynamic status information

ABSTRACT

A system and method for pacing rate control in a cardiac rhythm management (CRM) system. The method includes acquiring a pressure signal representative of coronary venous pressure (CVP) from a pressure sensor implanted within a coronary vein of the patient and generating a CVP waveform from the pressure signal. A pacing stimulus is applied to the patient&#39;s heart, and the pacing rate is increased in response to increases in patient&#39;s metabolic demand. The CVP index is monitored during the pacing rate increase, and the CRM system detects a reduction in the patient&#39;s hemodynamic performance based on the CVP index and establishes a maximum rate setting based on the pacing rate corresponding to the reduction in the patient&#39;s hemodynamic performance.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit under 35 U.S.C. §119 of U.S.Provisional Application No. 61/182,896, filed Jun. 1, 2009, entitled“System and Method for Pacing Rate Control Utilizing Patient HemodynamicStatus Information,” which is incorporated herein by reference for allpurposes.

This application is also related to co-pending and commonly assignedU.S. Patent Publication No. 2010/0305649, filed on May 26, 2010, andentitled “System and Method for Decompensation Detection and TreatmentBased on Patient Hemodynamics,” which is incorporated herein byreference for all purposes.

TECHNICAL FIELD

The present invention relates to medical devices and methods for cardiacrhythm management. More specifically, the present invention relates tosystems and methods for automatically adjusting the operating parametersof a cardiac rhythm management system.

BACKGROUND

Implantable cardiac rhythm management (CRM) systems, includingpacemakers, implantable cardioverter/defibrillators (ICDs), and cardiacresynchronization therapy (CRT, CRT-D) devices have been used to delivereffective treatment to patients with serious cardiac arrhythmias. Inparticular, rate adaptive pacing systems are known which utilize dataobtained from various implantable sensors, e.g., activity sensors suchas accelerometers and minute ventilation sensors, to adjust pacingparameters in response to increased patient demand. Despite significanttechnological advances in rate adaptive pacing technologies in recentyears, there exists a continuing need for improved pacing systems andmethods, particularly for use in patients suffering from congestiveheart failure (CHF).

SUMMARY

The present invention, in one embodiment, is a method of operating animplanted rate adaptive cardiac rhythm management system in a patient.The method comprises acquiring a pressure signal representative ofcoronary venous pressure (CVP) from a pressure sensor implanted within acoronary vein of the patient and generating a CVP waveform from thepressure signal, and applying a pacing stimulus to the patient's heart,the pacing stimulus being defined by a set of pacing parametersincluding a pacing rate. The method further comprises acquiring a signalrepresentative of the patient's metabolic demand from at least oneimplanted sensor, and monitoring a CVP index derived from the CVPwaveform while increasing the pacing rate in response to an increase inthe patient's metabolic demand. Additionally, the method comprisesdetecting a reduction in the patient's hemodynamic performance based onthe CVP index resulting from increasing the pacing rate and establishinga maximum rate setting based on the pacing rate corresponding to thereduction in the patient's hemodynamic performance, wherein the maximumrate setting delimits further metabolic demand-induced pacing rateincreases.

In another embodiment, the present invention is a method of operating animplanted cardiac rhythm management system in a patient. The methodcomprises acquiring a pressure signal indicative of coronary venouspressure (CVP) from a pressure sensor implanted within a coronary veinof the patient and deriving a selected CVP index from the pressuresignal, and calculating a baseline CVP index value. The method furthercomprises applying a pacing stimulus to the patient's heart, the pacingstimulus defined by a set of pacing parameters including a maximum ratesetting, and acquiring a signal representative of the patient'smetabolic demand from at least one implanted sensor. Additionally, themethod comprises, responsive to an increase in the patient's metabolicdemand, increasing the pacing rate and the maximum rate setting whilemonitoring the CVP index. The method further comprises detecting areduction in the patient's hemodynamic performance based on a change,relative to the CVP index baseline value, in the CVP index resultingfrom increasing the pacing rate and maintaining the maximum rate settingat a pacing rate below the pacing rate corresponding to the detectedreduction in the patient's hemodynamic performance.

In yet another embodiment, the present invention is an implantable rateadaptive cardiac rhythm management system configured for applying pacingstimuli to a patient's heart, the pacing stimuli defined by pacingparameters including a pacing rate and a maximum rate setting. Thesystem comprises a plurality of implantable medical electrical leadsconfigured to sense cardiac electrical activity and to deliver thepacing stimuli. At least one of the leads is configured for chronicimplantation within a coronary vein of the patient's heart and includesa pressure sensor configured to generate a coronary venous pressure(CVP) signal indicative of fluid pressure within the coronary vein. Thesystem further comprises an implantable pulse generator operativelycoupled to the leads configured to generate the pacing stimuli. Thepulse generator includes a control system configured to generate a CVPwaveform based on the pressure signal and derive a CVP index therefrom,and detect reductions in the patient's hemodynamic performance based onthe CVP index caused by an increase in the pacing rate. The controlsystem is further configured to adaptively adjust the pacing rate andthe maximum rate setting in response to changes in the patient'smetabolic demand. During use, the maximum rate setting is selectivelydefined by the control system based on the pacing rate corresponding tothe identified reduction in the patient's hemodynamic performance.

While multiple embodiments are disclosed, still other embodiments of thepresent invention will become apparent to those skilled in the art fromthe following detailed description, which shows and describesillustrative embodiments of the invention. Accordingly, the drawings anddetailed description are to be regarded as illustrative in nature andnot restrictive.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of an implantable cardiac rhythmmanagement (CRM) system according to one embodiment of the presentinvention in a deployed configuration.

FIG. 2 is a block diagram illustrating functional components of theimplantable CRM system of FIG. 1.

FIG. 3 is a chart schematically depicting cardiac output and selectedhemodynamic performance indicators as a function of heart rate.

FIG. 4 is an illustration of coronary venous system pressure waveformsthat can be obtained utilizing the CRM system of FIG. 1.

FIG. 5 is an illustration depicting a coronary venous pressure waveformand corresponding left ventricular pressure waveform.

FIG. 6 is a flow chart illustrating an exemplary method of controllingpacing settings for the CRM system of FIG. 1 according to one embodimentof the present invention.

FIG. 7 is a flow chart illustrating a method of controlling pacingparameters for the CRM system of FIG. 1 according to another embodimentof the present invention.

While the invention is amenable to various modifications and alternativeforms, specific embodiments have been shown by way of example in thedrawings and are described in detail below. The intention, however, isnot to limit the invention to the particular embodiments described. Onthe contrary, the invention is intended to cover all modifications,equivalents, and alternatives falling within the scope of the inventionas defined by the appended claims.

DETAILED DESCRIPTION

FIG. 1 is a schematic drawing of an implantable cardiac rhythmmanagement (CRM) system 10 according to one embodiment of the presentinvention, shown in a deployed state. As shown in FIG. 1, the CRM system10 includes a pulse generator 12 coupled to a cardiac lead system 13including a pair of medical electrical leads 14, 16 deployed in apatient's heart 18, which includes a right atrium 20 and a rightventricle 22, a left atrium 24 and a left ventricle 26, a coronary sinusostium 28 in the right atrium 20, a coronary sinus 30, and variouscoronary veins including an exemplary branch vessel 32 off of thecoronary sinus 30. As discussed in detail below, the CRM system 10 isconfigured to treat cardiac arrhythmias in a patient suffering from CHF.More specifically, the CRM system 10 is a rate adaptive pacing systemconfigured to adjust the pacing rate in response to changes in thepatient's sensed metabolic demand, and utilizes hemodynamic performanceinformation based on the output from implanted pressure sensors tofurther optimize the pacing system parameters. In various embodiments,the pressure sensors provide information that is indicative of orcorrelates closely to the patient's left ventricular pressure (LVP),which is a useful measure as an indicator of cardiac function inpatients suffering from CHF.

As shown in FIG. 1, the lead 14 includes a proximal portion 42 and adistal portion 36, which as shown is guided through the right atrium 20,the coronary sinus ostium 28 and the coronary sinus 30, and into thebranch vessel 32 of the coronary sinus 30. The distal portion 36 furtherincludes pressure sensors 38, 39, and an electrode 40. As shown, thepressure sensor 39 and the electrode 40 are positioned on the lead 14such that, when implanted, they are both located within the branchvessel 32. As further shown, the pressures sensor 38 is positioned onthe lead 14 such that, when implanted, it is located within the rightatrium 20. The illustrated position of the lead 14 may be used fordelivering a pacing and/or defibrillation stimulus to the left side ofthe heart 18. Additionally, the lead 14 may also be partially deployedin other regions of the coronary venous system, such as in the greatcardiac vein or other branch vessels for providing therapy to the leftside or right side of the heart 18.

In the illustrated embodiment, the electrode 40 is a relatively small,low voltage electrode configured for sensing intrinsic cardiacelectrical rhythms and/or delivering relatively low voltage pacingstimuli to the left ventricle 26 from within the branch coronary vein32. In various embodiments, the lead 14 can include additionalpace/sense electrodes for multi-polar pacing and/or for providingselective pacing site locations.

As further shown, in the illustrated embodiment, the lead 16 includes aproximal portion 34 and a distal portion 44 implanted in the rightventricle 22. In other embodiments, the CRM system 10 may include stilladditional leads, e.g., a lead implanted in the right atrium 20. Thedistal portion 44 further includes a flexible, high voltage electrode46, a relatively low-voltage ring electrode 48, and a low voltage tipelectrode 50 all implanted in the right ventricle 22 in the illustratedembodiment. The high voltage electrode 46 has a relatively large surfacearea compared to the ring electrode 48 and the tip electrode 50, and isthus configured for delivering relatively high voltage electricalstimulus to the cardiac tissue for defibrillation/cardioversion therapy,while the ring and tip electrodes 48, 50 are configured as relativelylow voltage pace/sense electrodes. The electrodes 48, 50 provide thelead 16 with bi-polar pace/sense capabilities.

In various embodiments, the lead 16 includes additionaldefibrillation/cardioversion and/or additional pace/sense electrodespositioned along the lead 16 so as to provide multi-polardefibrillation/cardioversion capabilities. In one exemplary embodiment,the lead 16 includes a proximal high voltage electrode in addition tothe electrode 46 positioned along the lead 16 such that it is located inthe right atrium 20 (and/or superior vena cava) when implanted.Additional electrode configurations can be utilized with the lead 16. Inshort, any electrode configuration can be employed in the lead 16without departing from the intended scope of the present invention.

In various embodiments, the lead 14 can be configured according to thevarious embodiments described in co-pending and commonly assigned U.S.Provisional Patent Application 61/088,270 titled “Implantable Lead andCoronary Venous Pressure Sensor Apparatus and Method” to Liu, et al. orcommonly assigned U.S. Pat. No. 7,409,244 titled “Method and Apparatusfor Adjusting Interventricular Delay Based on Ventricular Pressure,” toSalo, et al., the disclosures of which are incorporated herein byreference in their entireties. In other embodiments, the lead 14 withpressure sensor 39 and/or 38 can have other suitable configurations.

The pulse generator 12 is typically implanted subcutaneously within animplantation location or pocket in the patient's chest or abdomen. Thepulse generator 12 may be any implantable medical device known in theart or later developed, for delivering an electrical therapeuticstimulus to the patient suitable for treating cardiac tachyarrhythmias.In various embodiments, the pulse generator 12 is a pacemaker, animplantable cardioverter defibrillator (ICD) or a cardiacresynchronization (CRT) device configured for bi-ventricular pacing andincluding defibrillation capabilities (i.e., a CRT-D device). While notshown in FIG. 1, the pulse generator 12 includes hardware, software, andcircuitry operable as a detection/energy delivery system configured toreceive cardiac rhythm signals from the lead electrode(s) 40, 48, 50 andpressure signals from the pressure sensor(s) 38, 39, and also to delivera therapeutic electrical stimulus to the electrodes 40, 48, 50.

In various embodiments, the CRM system 10 further includes an additionallead deployed in the right atrium 20, which lead may include one or moreadditional electrodes sensing intrinsic cardiac signals and/ordelivering electrical stimuli to the cardiac tissue within the rightatrium 20.

The pressure sensor 39 is operable to sense and to generate anelectrical signal representative of a fluid pressure parameter withinthe coronary vein 32 in which it is implanted. The pressure sensor 39can be any device, whether now known or later developed, suitable forsensing pressure parameters within the coronary venous system andgenerating and transmitting a signal indicative of such pressureparameters to another device, e.g., the pulse generator 12. In variousembodiments, the pressure sensor 39 is configured to sense and generatea signal indicative of hydrostatic pressure within the coronary vein. Invarious embodiments, the pressure sensor 39 can be amicro-electrical-mechanical system (MEMS) device, which utilizessemiconductor techniques to build microscopic mechanical structures in asubstrate made from silicon or similar materials. In variousembodiments, the pressure sensor 39 can include a micro-machinedcapacitive or piezoresistive sensor exposed to the bloodstream. Otherpressure sensor technologies, such as resistive strain gages, are knownin the art and can also be employed as a pressure sensor 39.

In other exemplary embodiments, the pressure sensor 39 can include oneor more piezoelectric elements. Such piezoelectric elements areconfigured to flex and/or deflect in response to changes in pressurewithin the coronary vein in which it is implanted, and to generate anoutput current or voltage proportional to the corresponding pressurechange. In such embodiments, the pressure sensor 39 may advantageouslybe configured to sense fluid characteristics indicative of changes incoronary venous pressure during the cardiac cycle, e.g., dp/dt, which inturn can be monitored over time.

FIG. 2 is a schematic functional block diagram of an embodiment of theimplantable medical system 10. As shown in FIG. 2, the system 10 isdivided into functional blocks. The illustrated configuration isexemplary only, and there exist many possible configurations in whichthese functional blocks can be arranged. The example depicted in FIG. 2is one possible functional arrangement. The system 10 includes circuitryfor receiving cardiac electrical signals, coronary venous pressuresignals, and in some embodiments, right atrial pressure signals from theheart 18 and generating and delivering electrical energy in the form ofpace pulses or cardioversion/defibrillation pulses to the heart 18.

As discussed above, the cardiac lead system 13, which includes the leads14, 16 may be implanted so that the cardiac electrodes 40, 48, 50 (seeFIG. 1) contact heart tissue. The cardiac electrodes of the lead system13 sense cardiac signals associated with electrical activity of theheart. In addition, the pressure sensors 38, 39 on the lead 14 detectand generate pressure signals indicative of blood pressure within theright atrium 20 and coronary vein 32, respectively. The sensed cardiacsignals and pressure signals are transmitted to a the pulse generator 12through the lead system 13. The cardiac electrodes and lead system 13may be used to deliver electrical stimulation generated by the pulsegenerator 12 to the heart to mitigate various cardiac arrhythmias. Thepulse generator 12, in combination with the cardiac electrodes and thelead system 13, may detect cardiac signals and deliver therapeuticelectrical stimulation to any of the left and right ventricles and leftand right atria, for example.

As shown, the pulse generator 12 includes circuitry encased in ahermetically sealed housing 70 suitable for implanting in a human body.Power is supplied by a battery 72 that is housed within the housing 70.In one embodiment, the pulse generator circuitry is a programmablemicroprocessor-based system, including a control system 74, sensingcircuitry 76, therapy circuitry 78, communications circuitry 80, andmemory 82. The memory 82 may be used, for example, to store programmedinstructions for various pacing and defibrillation therapy and sensingmodes, and also data associated with sensed cardiac signals or otherphysiologic data, e.g., blood pressure. The parameters and data storedin the memory 82 may be used on-board for various purposes and/ortransmitted via telemetry to an external programmer unit 84 or otherpatient-external device, as desired. In various embodiments, the storeddata can be uploaded by a clinician and/or transmitted over an advancedpatient management (APM) system, such as the LATITUDE® system marketedby Boston Scientific Corporation.

The communications circuitry 80 allows the pulse generator 12 tocommunicate with the external programmer unit 84 and/or otherpatient-external system(s). In one embodiment, the communicationscircuitry 80 and the programmer unit 84 use a wire loop antenna and aradio frequency telemetric link to receive and transmit signals and databetween the programmer 84 and communications circuitry 80. In thismanner, programming commands may be transferred to the pulse generator12 from the programmer 84 during and after implantation. In addition,stored cardiac data may be transferred to the programmer unit 84 fromthe pulse generator 12, for example.

The sensing circuitry 76 detects cardiac signals sensed at the cardiacelectrodes 40, 48, 50, as well as blood pressure signals generated bythe pressure sensors 38, 39, and signals indicative of patient activityfrom implanted activity sensors 85, which provide information relatingto the patient's metabolic demand. The sensing circuitry 76 may include,for example, amplifiers, filters, A/D converters and other signalprocessing circuitry. Cardiac signals and pressure signals processed bythe sensing circuitry may be communicated to the control system 74.

The therapy circuitry 78 is controlled by the control system 74 and maybe used to deliver therapeutic stimulation pulses to the heart throughone or more of the cardiac electrodes, according to a pre-establishedpacing regimen under appropriate conditions. Thus, in variousembodiments, the therapy circuitry 78 is configured to deliver pacingstimuli to the right side and, in the case of a CRT or CRT-D system suchas the CRM system 10, also to the left side of the heart 18. In variousembodiments, the therapy circuitry 78 is also configured to deliveranti-tachycardia therapy stimuli to the ventricles and/or the atria.Such therapies may include, without limitation, relatively low-energyanti-tachycardia pacing pulses as well as high-energy shocks to treatand disrupt ventricular fibrillation episodes.

The control system 74 is used to control various subsystems of the pulsegenerator 12, including the therapy circuitry 78 and the sensingcircuitry 76. The control system 74 perform various functions,including, for example, arrhythmia analysis and therapy selection. Anarrhythmia analysis section of the control system 74 may compare signalsdetected through the sensing circuitry 76 to detect or predict variouscardiac arrhythmias, and to assist selection of appropriate therapiesfor the patient.

The control system 74 is also configured to adaptively adjust pacingparameters in response to changes in the patient's metabolic demand due,for example, to changes in the patient's physical activity. In thisregard, the control system 74 analyzes signals from the patient activitysensors 85 to determine whether pacing parameters, in particular, thepacing rate, should be increased or decreased in response to increasesor decreases, respectively, in the patient's metabolic demand. Asexplained in detail below, according to various embodiments of thepresent invention, the control system 74 is also configured to utilizepressure signals from the pressure sensors 38, 39 in adjusting pacingrates based on increases in the patient's metabolic demand.

As discussed above, LVP is a useful indicator of hemodynamic performancein patients with CHF. In particular, LVP can provide an indication as toworsening hemodynamic conditions, including a decrease in cardiac output(CO), as a result of an increase in the patient's heart rate.

FIG. 3 is a schematic graphical illustration showing cardiac output (CO)and two LVP parameters—LV pulse pressure (LV-PP) and LV end diastolicpressure (LV-EDP)—as a function of increasing heart rate. As shown inFIG. 3, a patient's (particularly CHF patient's) response to increasingheart rate, whether intrinsically driven or paced or both, typically hasa bimodal response. That is, as shown in FIG. 3, CO generally increasesinitially with increasing heart rate (Phase I in FIG. 3), then plateaus(Phase II), and then begins to decrease (Phase III). Thus, while it isdesirable to increase heart rate, e.g., by increasing a pacing rate, tomatch an increase in metabolic demand due to an increase in patientactivity, it is also desirable to avoid driving the patient's heart intothe zone in FIG. 3 indicated by decreasing CO. As such, rate adaptivepacing protocols generally include one or more maximum rate settings tolimit the maximum allowable pacing rate so as to avoid adverselyimpacting CO in situations where the patient's metabolic demand wouldotherwise dictate further increases in the pacing rate.

Two such maximum rate settings are the maximum sensor rate (MSR) and themaximum tracking rate (MTR). As is generally known, MSR and MTR areclosely related, but not identical, pacing parameters. That is, MSR isthe maximum pacing rate allowed as a result of sensor control (e.g.,from an accelerometer or other activity sensor input), while MTR is themaximum ventricular paced rate that is allowed in response to sensedatrial rhythms. In either case, pacing above the MSR or MTR limit themaximum pacing rate in response to sensed events.

In conventional pacing systems lacking direct hemodynamic statusinformation inputs, the MSR/MTR are generally programmed by theclinician based on empirical information regarding the patient. Oftenthe clinician will set these parameters well below the range at whichhemodynamic compromise would be expected to occur due to increasedpacing rates. As a result, the pacing rate may be unnecessarily limitedin situations where the patient's metabolic demand would otherwise callfor an increase in the pacing rate and the patient's hemodynamic statusis not materially compromised due to the increased rate.

Thus, in an embodiment of the present invention, the CRM system 10utilizes hemodynamic performance information to adaptively adjust theMSR and/or MTR so as to accommodate increases in the patient's metabolicdemand.

As discussed above, FIG. 3 also illustrates changes in exemplary LVPparameters—LV pulse pressure (LV-PP) and LV end diastolic pressure(LV-EDP)—as a function of increasing heart rate. As shown in FIG. 3,increases in heart rate also affect the LV-PP and LV-EDP. In particular,the shape of the LV-PP curve generally tracks the shape of the CO curveas the patient's heart rate increases, such that the LV-PP initiallyincreases with increasing heart rate, then plateaus, and subsequentlybegins to decline as the heart rate further increases. Additionally, asfurther shown in FIG. 3, the LV-EDP is initially relatively constant asthe heart rate increases, then rises relatively sharply. Thus,information indicative of the patient's LV-PP and/or LV-EDP can beutilized by the CRM system 10 to adaptively adjust the MSR/MTR tooptimize rate adaptive pacing in response to patient metabolic demandincreases.

For example, an LV-PP waveform such as shown in FIG. 3 can provide anindication as to when the patient's hemodynamic status begins to worsenas a result of an increase in pacing/heart rate. That is, a decrease inLV-PP accompanying an increase in pacing rate can indicate acorresponding decrease in CO, and further pacing rate increases, even asmetabolic demand continues to increase, can be avoided. Similarly, anLV-EDP waveform such as shown in FIG. 3 can also be generated and theslope of this waveform can be determined. As is apparent from FIG. 3, anincrease in the slope of the LV-EDP curve can be used to limit furtherincreases in pacing rate. Alternatively, a change in the average LV-EDPvalue during the rate increase relative to a baseline LV-EDP value(derived prior to the start of the rate increase) can be calculated andmonitored. Accordingly, the pacing rate can be limited where therelative change in average LV-EDP compared to the baseline value exceedsa threshold value,

LV-PP and LV-EDP are only illustrative of the LV pressure parametersthat can be estimated to assess the patient's hemodynamic status. Otherexemplary parameters include, without limitation, LV systolic pressure(LV-SP), mean LVP, and LV dp/dt.

However, obtaining direct LV pressure information chronically is bothtechnically and clinically challenging. Accordingly, in variousembodiments, as described in detail below, coronary venous pressure(CVP) is utilized as a surrogate for direct LVP measurement. Asexplained above, the pressure sensors 38, 39 are configured to detectand generate pressure signals representative of fluid pressure withinthe right atrium 20 and the coronary vein 36, respectively. From thesepressure signals, pressure waveforms can be derived and evaluated by thesensing circuitry 76 and the control system of the pulse generator 12.FIG. 4 illustrates pressure waveforms obtained from the right atrium(RA), left ventricle (LV), coronary sinus (CS) and various locations ina coronary vein (CV) in an exemplary animal study. As shown, thecoronary venous pressure (CVP) waveform takes on the same general shapeas the LV waveform, particularly where the CVP is taken from a locationlower in the coronary vein, i.e., as indicated by the “Wedged” (apicaltwo-thirds) CV pressure graph.

FIG. 5 is an illustration depicting a CVP waveform and a correspondingLVP waveform also obtained in an exemplary animal study. As can be seenin FIG. 5, the CVP and LVP waveforms correlate closely to one another.Thus, in view of the close correlation between coronary venous pressureand LV pressure, CVP can function as a surrogate for LVP in the CRMsystem 10, which can then derive one or more CVP indexes that closelycorrelate to corresponding LVP indexes, and can thus be utilized in thesame manner as the LVP indexes to adaptively adjust maximum pacing ratesettings, e.g., MSR/MTR, in response to changes in the patient'smetabolic demand.

Thus, in one embodiment, an exemplary CVP index used by the CRM system10 is based on CVP pulse pressure (CVP-PP), which as will be apparent inview of FIGS. 4 and 5 and the corresponding discussion, will correlateclosely to LVP-PP. In this case, the control system 74 can generate aCVP waveform based on the pressure signal obtained from the pressuresensor 39, and from this waveform can derive a secondary waveformtracking CV-PP over time. From this, an appropriate CVP index, such asan average CV-PP value over a specified interval, or a direct CV-PPvalue itself, can be monitored by the control system 74 for establishingpacing rate settings. Similarly, coronary venous end diastolic pressure(CV-EDP) will also correlate closely to LV-EDP, and thus the CVP indexcan also be based on CV-EDP and utilized by the control system 74 toestablish maximum pacing rate settings.

FIG. 6 is a flow chart illustrating one method 200 of pacing parametercontrol that can be accomplished by the CRM system 10 according to oneembodiment of the present invention. As shown in FIG. 6, the method 200begins with the CRM system 10 acquiring a pressure signal representativeof CVP, from which the control system 74 generates a CVP waveform (block210). As further shown in FIG. 6, the method 200 contemplates that apacing stimulus is applied to the patient's heart by the CRM system 10(block 220). Additionally, the CRM system acquires one or more signalsrepresentative of the patient's metabolic demand from an implantedsensor (block 230). Such sensors can include, without limitation,activity sensors such as accelerometers and minute ventilation sensors,which are well known in the art and are thus not discussed in furtherdetail here.

As further shown in FIG. 6, the CRM system 10 monitors a CVP index (or aplurality of indexes) derived from the CVP waveform while concurrentlyincreasing the pacing rate in response to increased metabolic demand(block 240). For example, if the patient's physical activity increases,the resulting increase in the patient's metabolic demand will bedetected by the CRM system 10, which will in turn initiate an increasein the pacing rate according to a protocol programmed by the clinician.

The selected CVP index(es) can be any index correlating to an LVPparameter indicative of the patient's hemodynamic performance. That is,in various embodiments, the CVP index is based on CV-PP, CV-EDP, CV-SP,CV dp/dt, and the like. In various embodiments, the CVP index may bederived directly from the CVP waveform, e.g., as a secondary waveformbased on a CV parameter such as CV-PP or CV-EDP calculated on abeat-by-beat basis, or it may itself be calculated from such values,e.g., as an average value over a selected interval (e.g., a selectednumber of beats, or a selected time interval).

As further shown in FIG. 6, the method 200 further includes detecting areduction (or an impending reduction) in the patient's hemodynamicperformance, based on the CVP index, as a result of the increase in thepacing rate in response to the increased metabolic demand (block 250).The control system 74 in turn establishes a maximum pacing rate setting(e.g., MSR/MTR setting) based on the pacing rate corresponding to thepoint at which hemodynamic performance begins to decrease. For example,in one embodiment, control system 74 is configured to define the maximumrate setting at a predetermined percentage of or below the pacing rateat which the reduction of hemodynamic performance is detected. Inanother embodiment, the control system 74 is configured to set themaximum rate setting at a certain number of beats/minute below thepacing rate at which the reduction of hemodynamic performance isdetected. Still other criteria for establishing the maximum rate settingupon the detection of a decrease in hemodynamic performance may beemployed. In all cases, the CVP data obtained from the implantedpressure sensor(s) provide a means for the control system 74 todynamically adjust the maximum pacing rate limits for the CRM system 10based on actual patient hemodynamic status feedback.

The particular CVP index utilized can be any CVP index providing a closecorrelation to a hemodynamically significant LVP parameter. For example,the control system 74 may, in one embodiment, monitor CV-PP as thepacing rate is increased in response to increased metabolic demand.Referring back to FIG. 3, because CV-PP closely correlates with LV-PP,the shape of a CV-PP waveform as a function of heart/pacing rate willtake on the same general shape as the LV-PP waveform illustrated in FIG.3. Thus, if the control system 74 detects a CV-PP waveform during aperiod of increasing pacing rate characterized by an initial increase inCV-PP, followed by a generally constant CV-PP and in turn by a decreasein CV-PP, the point at which the CV-PP begins to decrease will generallysignify a reduction, or at least an impending reduction, in thepatient's hemodynamic performance. Alternatively, the control system 74may be configured to associate a decrease in CV-PP during a period ofincreasing heart rate (without regard to the preceding CV-PP behavior)as an indication of a reduction in hemodynamic performance.

In another embodiment, the CV-EDP provides the basis for the CVP indexutilized by the control system 74 in the method 200. For example, theCV-EDP can be determined based on the CVP waveform (e.g., on abeat-by-beat basis, or as an average CV-EDP over a selected timeinterval, number of beats, etc.), and then monitored by the controlsystem 74 as the pacing rate is increased in response to changes inmetabolic demand. In one embodiment, the control system 74 generates asecondary CVP waveform as a function of time or heart/pacing rate.Referring back to FIG. 3, the control system 74 can then monitor changesin the slope of the CV-EDP waveform, whereby a substantial increase inthe slope accompanying an increase in pacing rate indicates a reduction(or impending reduction) in hemodynamic performance as a result of thepacing rate increase. The CV-EDP slope increase associated with adecrease in hemodynamic performance can, for example, be a programmedvalue determined based on the patient's clinical history or needs.

Still other CVP indexes, e.g., based on CV dp/dt, CV-SP, etc., may beused by the control system 74 in addition to or in lieu of the CV-PPand/or CV-EDP values discussed above. FIG. 7 is a flow chartillustrating a method 300 of controlling pacing parameters of the CRMsystem 10 according to another embodiment of the present invention. Asshown in FIG. 7, the method 300 begins with the control system 74 of theCRM system 10 acquiring a pressure signal representative of CVP andderiving a CVP index from the pressure signal (block 310). The controlsystem 74 then calculates a baseline CVP index value (block 320). Thebaseline CVP index value can be calculated at any appropriate interval.In one embodiment, the baseline CVP index value is based on CVP dataduring a steady state operation of the CRM system prior to theinitiation of a pacing rate increase in response to changes in metabolicdemand. The baseline can be based on a single cycle, or alternatively,may be an average value over a preselected time interval or apredetermined number of cardiac beats.

As with the method 200 described above, the method 300 furthercontemplates that a pacing stimulus is applied to the patient's heart bythe CRM system 10 (block 330). In one embodiment, pacing parameters forthe pacing stimulus include a pacing rate and a maximum rate setting(e.g., MSR and/or MTR). Additionally, the CRM system acquires one ormore signals representative of the patient's metabolic demand from animplanted sensor, as described above (block 340).

As further shown in FIG. 7, the CRM system 10 concurrently monitors theCVP index (or a plurality of indexes) and increases the pacing rate andmaximum rate setting in response to increased metabolic demand (block350). Subsequently, the method 300 further includes detecting, based onthe CVP index, a reduction (or an impending reduction) in the patient'shemodynamic performance as a result of the increase in the pacing ratein response to the increased metabolic demand (block 360). Upondetecting the reduction in hemodynamic performance, the control system74 maintains the maximum rate setting at a pacing rate at or below(i.e., within a predefined percentage or beats/minute of) the pacingrate above which any further increase in pacing rate leads to thedecrease (or impending decrease) in the patient's hemodynamicperformance (block 370).

In the method 300, the CVP index corresponding to the increasing pacingrate is compared to the baseline CVP index value to detect or predictthe onset of a decrease in hemodynamic function. In one embodiment, thecontrol system 74 is configured to define a change in the CVP indexvalue (calculated at increased pacing rates due to increased metabolicdemand) relative to the baseline CVP index value that exceeds apredetermined threshold amount as an indicator of a decrease inhemodynamic function.

For example, the CVP index can be based on changes in the CV-EDP duringmetabolic demand-induced pacing rate increases. In this case, forexample, the control system 74 will calculate a rolling average CV-EDPvalue during the pacing rate increase period and compare this rollingaverage CV-EDP to the baseline CV-EDP value calculated prior to the rateincrease. If the difference between any rolling average CV-EDP value andthe baseline value does not exceed a predetermined threshold amount, thecontrol system will continue to allow the pacing rate to increase inresponse to further increases in metabolic demand. If, however, thedifference between the rolling average CV-EDP value during the rateincrease exceeds the predetermined threshold, the control system 74 willidentify this situation as indicative of a reduction in CO or some otherhemodynamic performance parameter, and will set the maximum rate settingaccordingly.

Additional enhancements can be incorporated into either of the methods200 or 300 described above. For example, upon establishing the maximumrates setting in response to the detection of hemodynamic performancereduction as described above, the CRM system 10 can be programmed tore-open the monitoring window, e.g., after a predetermined time periodat an elevated pacing rate, to determine whether the patient'shemodynamic state has stabilized to the point where the patient cantolerate further pacing rate increases in response to continuedincreased metabolic demand. In addition, in various embodiments, thepressures sensor 38 (see FIG. 1) detects and generates a signalindicative of right atrial pressure and right ventricular fillingpressure (RV-EDP), which can be a useful indication for rightventricular hemodynamics and can also be used by the control system 74in conjunction with the CVP indexes discussed above for establishing themaximum pacing rate settings.

Thus, the various embodiments of the present invention provide fordynamic adjustment of pacing rate limits by the implanted CRM system 10,so as to improve the ability of the CRM system 10 to accommodate thepatient's metabolic demands while substantially maintaining thepatient's hemodynamic performance. The CRM system 10 thus providesoperational advantages, particularly when used with patients diagnosedwith CHF, where the pacing rate limits may otherwise need to be set atartificially low settings to avoid unintentionally reducing thepatient's hemodynamic performance.

Various modifications and additions can be made to the exemplaryembodiments discussed without departing from the scope of the presentinvention. For example, while the embodiments described above refer toparticular features, the scope of this invention also includesembodiments having different combinations of features and embodimentsthat do not include all of the described features. Accordingly, thescope of the present invention is intended to embrace all suchalternatives, modifications, and variations as fall within the scope ofthe claims, together with all equivalents thereof.

We claim:
 1. A method of operating an implanted rate adaptive cardiacrhythm management system in a patient, the method comprising: acquiringa pressure signal representative of coronary venous pressure (CVP) froma pressure sensor implanted within the lower apical two thirds of acoronary vein of the patient and generating a CVP waveform therefrom;applying a pacing stimulus to the patient's heart, the pacing stimulusdefined by a set of pacing parameters including a pacing rate; acquiringa signal representative of the patient's metabolic demand from at leastone implanted sensor; monitoring a CVP index derived from the CVPwaveform while increasing the pacing rate in response to an increase inthe patient's metabolic demand, wherein the CVP index is based oncoronary venous pulse pressure (CV-PP) sensed by the pressure sensor;detecting a reduction in the patient's hemodymanic performance based onthe CVP index resulting from increasing the pacing rate; andestablishing a maximum rate setting based on the pacing ratecorresponding to the reduction in the patient's hemodynamic performance,wherein the maximum rate setting delimits further metabolicdemand-induced pacing rate increases.
 2. The method of claim 1 whereinestablishing the maximum rate setting includes defining the maximum ratesetting as a pacing rate above which any further increase in pacing rateleads to the reduction in the patient's hemodynamic performance.
 3. Themethod of claim 1 wherein establishing the maximum rate setting includesdefining the maximum rate setting as a pacing rate below, by apredetermined amount, a pacing rate above which any further increase inpacing rate leads to the reduction in the patient's hemodynamicperformance.
 4. The method of claim 1 wherein the predetermined amountis a predetermined number of beats per minute or a predeterminedpercentage.
 5. The method of claim 1 wherein monitoring the CVP indexincludes generating a waveform of average CV-PP values as a function ofthe pacing rate during a period in which the pacing rate is increased inresponse to increased metabolic demand.
 6. The method of claim 5 whereindetecting the reduction in the patient's hemodymanic performanceincludes detecting a reduction in the patient's average CV-PP during theperiod in which the pacing rate is increased in response to increasedmetabolic demand.
 7. The method of claim 6 wherein establishing themaximum rate setting includes establishing the maximum rate settingbased on the pacing rate corresponding to the reduction in the patient'saverage CV-PP value.
 8. The method of claim 1 wherein the CVP index is achange in a CV-PP, and wherein detecting the reduction in the patient'shemodymanic performance includes identifying a decrease in the CV-PPaccompanying the increase in the pacing rate in response to a metabolicdemand increase.
 9. The method of claim 1 wherein the maximum ratesetting is a maximum sensor rate (MSR) or maximum tracking rate (MTR).10. A method of operating an implanted cardiac rhythm management systemin a patient, the method comprising: acquiring a pressure signalindicative of coronary venous pressure (CVP) from a pressure sensorimplanted within the lower apical two thirds of a coronary vein of thepatient and deriving a selected CVP index from the pressure signal;calculating a baseline CVP index value based on the pressure signal, theCVP index based on coronary venous end diastolic pressure (CV-EDP) ofthe CVP; applying a pacing stimulus to the patient's heart, the pacingstimulus defined by a set of pacing parameters including a maximum ratesetting; acquiring a signal representative of the patient's metabolicdemand from at least one implanted sensor; responsive to an increase inthe patient's metabolic demand, increasing the pacing rate and themaximum rate setting while monitoring the CVP index; and detecting areduction in the patient's hemodymanic performance based on a change,relative to the CVP index baseline value, in the CVP index resultingfrom increasing the pacing rate, wherein the change comprises anincrease in the slope of the CV-EDP; and maintaining the maximum ratesetting at a pacing rate below the pacing rate corresponding to thedetected reduction in the patient's hemodynamic performance.
 11. Themethod of claim 10 wherein the baseline CVP index value is derived priorto the pacing rate increase in response to the increase in the patient'smetabolic demand.
 12. The method of claim 11 wherein the CVP index is arolling average CV-EDP value during a period in which the pacing rate isincreased in response to the increase in the patient's metabolic demand.13. An implantable rate adaptive cardiac rhythm management systemconfigured for applying pacing stimuli to a patient's heart, the pacingstimuli defined by pacing parameters including a pacing rate and amaximum rate setting, the system comprising: a plurality of implantablemedical electrical leads configured to sense cardiac electrical activityand to deliver the pacing stimuli, at least one of the leads beingconfigured for chronic implantation within a coronary vein of thepatient's heart and including a pressure sensor configured to generate acoronary venous pressure (CVP) signal indicative of fluid pressure fromwithin the lower apical two thirds of a coronary vein; an implantablepulse generator operatively coupled to the leads configured to generatethe pacing stimuli, the pulse generator including a control systemconfigured to: generate a CVP waveform based on the pressure signal andderive a CVP index therefrom, wherein the CVP index is based on coronaryvenous pulse pressure (CV-PP) sensed by the pressure sensor; detectreductions in the patient's hemodynamic performance based on the CVPindex caused by an increase in the pacing rate; and adaptively adjustthe pacing rate and the maximum rate setting in response to changes inthe patient's metabolic demand, wherein during use, the maximum ratesetting is selectively defined by the control system based on the pacingrate corresponding to the identified reduction in the patient'shemodynamic performance.